Acute Modulation of Stereotyped High Frequency Oscillations with a Closed-Loop Brain Interchange System in Drug Resistant Epilepsy

项目总结:

Project Summary: High frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual and language cortices. In this project, we present the initial evidence of a recurrent waveform pattern that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, we show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. We hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier. If the first phase (Aim-1) of our study becomes successful, later in the second phase (Aim-2), once again in the EMU, we will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC. We will investigate the modulatory effects of this closed-loop stimulation strategy by monitoring the changes in signature events such as spikes, epileptic discharges, ripples and fast ripples. If successful, this closed-loop system does not have to wait for a seizure to start in order to deliver the stimulation at its onset as done by the RNS system of Neuropace. In contrast, the system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these areas to prevent seizures from occurring. If the outcomes of our research in acute setting become successful, we will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting. 1